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Updated: May 23, 2026

Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Cellular aspects of the distinct M protein and SfbI anchoring pathways in Streptococcus pyogenes
Assaf Raz1, Susanne R Talay, Vincent A Fischetti
1Bacterial Pathogenesis and Immunology, Rockefeller University, New York, USA. araz@rockefeller.edu
Abstract:
Wall-anchored surface proteins are critical for the in vivo survival of Streptococcus pyogenes. Cues in the signal sequence direct the membrane translocation of surface proteins: M protein to the septum, and SfbI to the poles. Both proteins are subsequently anchored to the wall by the membrane bound enzyme sortase A. However, the cellular features of these pathways are not fully understood. Here we show that M protein and SfbI are anchored simultaneously throughout the cell cycle. M protein is rapidly anchored at the septum, and in part of the cell cycle, is anchored simultaneously at the mother and daughter septa. Conversely, SfbI accumulates gradually on peripheral peptidoglycan, resulting in a polar distribution. Sortase is not required for translocation of M protein or SfbI at their respective locations. Methicillin-induced unbalanced peptidoglycan synthesis diminishes surface M protein but not SfbI. Furthermore, overexpression of the division regulator DivIVA also diminishes surface M protein but increases SfbI. These results demonstrate a close connection between the regulation of cell division and protein anchoring. Better understanding of the spatial regulation of surface anchoring may lead to the identification of novel targets for the development of anti-infective agents, given the importance of surface molecules for pathogenesis.
Insights
Surface proteins like M protein and SfbI are crucial for Streptococcus pyogenes survival. Their anchoring is linked to cell division, offering potential targets for new anti-infective agents.
Area of Science:
- Microbiology
- Cell Biology
- Bacterial Pathogenesis
Background:
- Surface proteins are essential for Streptococcus pyogenes survival in vivo.
- The precise mechanisms of surface protein translocation and anchoring are not fully elucidated.
- M protein and SfbI are key surface proteins targeted for anchoring by sortase A.
Purpose of the Study:
- To investigate the cellular features and spatial regulation of M protein and SfbI anchoring in Streptococcus pyogenes.
- To determine the relationship between cell division processes and surface protein anchoring.
- To explore potential novel targets for anti-infective agents based on surface anchoring mechanisms.
Main Methods:
- Simultaneous observation of M protein and SfbI anchoring throughout the cell cycle.
- Analysis of protein translocation independent of sortase A.
- Investigating the effects of methicillin-induced peptidoglycan synthesis changes.
- Examining the impact of DivIVA overexpression on surface protein levels.
Main Results:
- M protein and SfbI are anchored simultaneously across the cell cycle.
- M protein anchors rapidly at the septum, while SfbI gradually accumulates at the poles.
- Sortase A is not essential for the translocation of M protein or SfbI.
- Disruptions in peptidoglycan synthesis or cell division regulators affect M protein and SfbI anchoring differently.
Conclusions:
- Cell division regulation is closely interconnected with surface protein anchoring in Streptococcus pyogenes.
- Distinct spatial regulation mechanisms exist for M protein and SfbI anchoring.
- Understanding these anchoring pathways may reveal new targets for developing anti-infective therapies.
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